Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment

Abstract

Introduction: Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%-15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy.

Objectives: The Comparing Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial for acute appendicitis aims to determine whether the antibiotic treatment strategy is non-inferior to appendectomy.

Methods/analysis: CODA is a randomised, pragmatic non-inferiority trial that aims to recruit 1552 English-speaking and Spanish-speaking adults with imaging-confirmed appendicitis. Participants are randomised to appendectomy or 10 days of antibiotics (including an option for complete outpatient therapy). A total of 500 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary analytic outcome is quality of life (measured by the EuroQol five dimension index) at 4 weeks. Clinical adverse events, rate of eventual appendectomy, decisional regret, return to work/school, work productivity and healthcare utilisation will be compared. Planned exploratory analyses will identify subpopulations that may have a differential risk of eventual appendectomy in the antibiotic treatment arm.

Ethics and dissemination: This trial was approved by the University of Washington's Human Subjects Division. Results from this trial will be presented in international conferences and published in peer-reviewed journals.

Trial registration number: NCT02800785.

Keywords: adult surgery; appendicitis; patient-centred research; treatment options.

Figure 1

Example study conclusions in the Comparing Outcomes of Antibiotic Drugs and Appendectomy trial. There are four possible study conclusions. (A) The observed treatment effect (black circle) of antibiotics is almost zero and the 97.5% one-sided CI (arrow) does not overlap the non-inferiority margin of −5%, indicating that antibiotics is a non-interior strategy. (B) The observed treatment effect of antibiotics is more than 2.5% better than appendectomy and the CI does not include 0, indicating that antibiotics are superior. (C) The observed treatment effect of antibiotics is 2.5% worse than appendectomy but the CI includes −5%, so non-inferiority cannot be claims. (D) The observed treatment effect of antibiotics is more than 5% worse than appendectomy, indicating that antibiotics are inferior.